AB0723 Anti-TIF1-beta autoantibodies in a patient with cancer-associated dermatomyositis
Authors: J. B. Vulsteke, P. De Haes, M. Satoh, E. De Langhe, X. Bossuyt
Journal: Annals of the Rheumatic Diseases (2022)

Background Anti-transcriptional intermediary factor 1-gamma (TIF1-gamma) autoantibodies are strongly linked to cancer-associated dermatomyositis (DM). In addition to anti-TIF1-gamma autoantibodies, autoantibodies to TIF1-alpha and TIF1-beta have been described, often coexisting with TIF1-gamma or other known autoantibodies [1,2]. Thus far, anti-TIF1-beta autoantibodies without other known autoantibodies have been identified in only 3 patients with dermatomyositis, of which none had cancer [1,2]. Objectives To report on a patient with cancer-associated dermatomyositis and isolated anti-TIF1-beta autoantibodies. Methods Serum of a patient with cancer-associated dermatomyositis without known autoantibody specificity was evaluated by immunoprecipitation combined with liquid chromatography-tandem mass spectrometry (IP + LC-MS/MS). Mass spectrometry data were matched against the Uniprot Homo Sapiens database with the Mascot search engine using Proteome Discoverer. Additional immunoprecipitation of radiolabeled cell extract followed by autoradiography were performed. Clinical and laboratory data were retrieved from the electronic health record. Results TIF1-beta was identified in the immunoprecipitate of the serum of the patient by IP + LC-MS/MS, but not TIF1-gamma or TIF1-alpha. These results were confirmed by immunoprecipitation of radiolabeled cell extract (Figure 1A). The HEp-2 indirect immunofluorescence assay showed a nuclear fine speckled pattern (AC-4, maximum titre &gt; 1/1280, Figure 1B), which corresponds to the subcellular localization of TIF1-beta [3]. The patient, a 64-year old male, presented with dermatomyositis with classical cutaneous and muscular involvement (max. serum creatine kinase level 370 U/l). A renal cell carcinoma was found during the diagnostic work-up for which a partial nephrectomy was performed. There was a good response of both cutaneous and muscular disease activity to treatment with hydroxychloroquine and methylprednisolone. Figure 1. A Immunoprecipitation with 35 S-methionine labeled K562 cells with subsequent radiography. C Positive control with anti-TIF1-beta and anti-U1-RNP autoantibodies, 1 anti-TIF1-beta-positive patient (patient here described), 2 negative patient, 3 anti-TIF1-gamma/alpha-positive patient B Nuclear fine speckled pattern on HEp-2 indirect immunofluorescence assay, 40X magnification Conclusion Isolated anti-TIF1-beta autoantibodies should be considered in patients with dermatomyositis without known myositis-specific autoantibodies and can be associated with cancer. References [1]Fujimoto M, Hamaguchi Y, Kaji K, et al. Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins. Arthritis Rheum 2012; 64 :513–22. doi:10.1002/art.33403 [2]Satoh M, Chan JYF, Ross SJ, et al. Autoantibodies to transcription intermediary factor (TIF)1β associated with dermatomyositis. Arthritis Res Ther 2012; 14 :1–8. doi:10.1186/AR3802/FIGURES/2 [3]Thul PJ, Åkesson L, Wiking M, et al. A subcellular map of the human proteome. Science 2017; 356 . doi:10.1126/science.aal3321 Disclosure of Interests Jean-Baptiste Vulsteke: None declared, Petra De Haes: None declared, Minoru Satoh: None declared, Ellen De Langhe: None declared, Xavier Bossuyt Consultant of: Inova Diagnostics, Thermo Fisher Scientific